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Endogenous opioid peptides and brain development: Endomorphin-1 and Nociceptin play a sex-specific role in the control of oligodendrocyte maturation and brain myelination.
Glia ( IF 5.4 ) Pub Date : 2020-02-17 , DOI: 10.1002/glia.23799 Esraa Mohamed 1 , Caitlin E Paisley 1 , Logan C Meyer 1 , John W Bigbee 2 , Carmen Sato-Bigbee 1
Glia ( IF 5.4 ) Pub Date : 2020-02-17 , DOI: 10.1002/glia.23799 Esraa Mohamed 1 , Caitlin E Paisley 1 , Logan C Meyer 1 , John W Bigbee 2 , Carmen Sato-Bigbee 1
Affiliation
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The generation of fully functional oligodendrocytes, the myelinating cells of the central nervous system, is preceded by a complex maturational process. We previously showed that the timing of oligodendrocyte differentiation and rat brain myelination were altered by perinatal exposure to buprenorphine and methadone, opioid analogs used for the management of pregnant addicts. Those observations suggested the involvement of the μ-opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOR). However, it remained to be determined if these receptors and their endogenous ligands could indeed control the timing of myelination under normal physiological conditions of brain development. We now found that the endogenous MOR ligand endomorphin-1 (EM-1) exerts a striking stimulatory action on cellular and morphological maturation of rat pre-oligodendrocytes, but unexpectedly, these effects appear to be restricted to the cells from the female pups. Critically, this stimulation is abolished by coincubation with the endogenous NOR ligand nociceptin. Furthermore, NOR antagonist treatment of 9-day-old female pups results in accelerated brain myelination. Interestingly, the lack of sex-dependent differences in developmental brain levels of EM-1 and nociceptin, or oligodendroglial expression of MOR and NOR, suggests that the observed sex-specific responses may be highly dependent on important intrinsic differences between the male and female oligodendrocytes. The discovery of a significant effect of EM-1 and nociceptin in the developing female oligodendrocytes and brain myelination, underscores the need for further studies investigating brain sex-related differences and their implications in opioid use and abuse, pain control, and susceptibility and remyelinating capacity in demyelinating disease as multiple sclerosis.
中文翻译：
内源性阿片肽和大脑发育：Endomorphin-1 和痛敏肽在控制少突胶质细胞成熟和脑髓鞘形成中发挥性别特异性作用。
全功能少突胶质细胞（中枢神经系统的髓鞘形成细胞）的产生之前是一个复杂的成熟过程。我们之前表明，围产期暴露于丁丙诺啡和美沙酮（用于治疗怀孕成瘾者的阿片类药物类似物）会改变少突胶质细胞分化和大鼠脑髓鞘形成的时间。这些观察结果表明μ-阿片受体（MOR）和伤害感受肽/孤啡肽FQ受体（NOR）参与其中。然而，这些受体及其内源性配体是否确实可以在大脑发育的正常生理条件下控制髓鞘形成的时间仍有待确定。我们现在发现内源性 MOR 配体内吗啡肽-1 (EM-1) 对大鼠前少突胶质细胞的细胞和形态成熟具有显着的刺激作用，但出乎意料的是，这些作用似乎仅限于雌性幼崽的细胞。重要的是，这种刺激通过与内源性 NOR 配体伤害感受素共孵育而被消除。此外，对 9 日龄雌性幼崽进行 NOR 拮抗剂治疗会导致脑髓鞘形成加速。有趣的是，EM-1和伤害感受素的发育脑水平或MOR和NOR的少突胶质细胞表达缺乏性别依赖性差异，这表明观察到的性别特异性反应可能高度依赖于男性和女性少突胶质细胞之间重要的内在差异。 EM-1 和伤害感受素对发育中的雌性少突胶质细胞和脑髓鞘形成具有显着影响的发现，强调需要进一步研究调查大脑性别相关差异及其对阿片类药物使用和滥用、疼痛控制、敏感性和髓鞘再生能力的影响脱髓鞘疾病如多发性硬化症。
更新日期：2020-02-17
中文翻译：
内源性阿片肽和大脑发育：Endomorphin-1 和痛敏肽在控制少突胶质细胞成熟和脑髓鞘形成中发挥性别特异性作用。
全功能少突胶质细胞（中枢神经系统的髓鞘形成细胞）的产生之前是一个复杂的成熟过程。我们之前表明，围产期暴露于丁丙诺啡和美沙酮（用于治疗怀孕成瘾者的阿片类药物类似物）会改变少突胶质细胞分化和大鼠脑髓鞘形成的时间。这些观察结果表明μ-阿片受体（MOR）和伤害感受肽/孤啡肽FQ受体（NOR）参与其中。然而，这些受体及其内源性配体是否确实可以在大脑发育的正常生理条件下控制髓鞘形成的时间仍有待确定。我们现在发现内源性 MOR 配体内吗啡肽-1 (EM-1) 对大鼠前少突胶质细胞的细胞和形态成熟具有显着的刺激作用，但出乎意料的是，这些作用似乎仅限于雌性幼崽的细胞。重要的是，这种刺激通过与内源性 NOR 配体伤害感受素共孵育而被消除。此外，对 9 日龄雌性幼崽进行 NOR 拮抗剂治疗会导致脑髓鞘形成加速。有趣的是，EM-1和伤害感受素的发育脑水平或MOR和NOR的少突胶质细胞表达缺乏性别依赖性差异，这表明观察到的性别特异性反应可能高度依赖于男性和女性少突胶质细胞之间重要的内在差异。 EM-1 和伤害感受素对发育中的雌性少突胶质细胞和脑髓鞘形成具有显着影响的发现，强调需要进一步研究调查大脑性别相关差异及其对阿片类药物使用和滥用、疼痛控制、敏感性和髓鞘再生能力的影响脱髓鞘疾病如多发性硬化症。
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